Advances in functional nanomaterial interfaces for small-molecule metabolite sensing and wearable applications

Dynamic metabolic changes provide functional information that cannot be captured by a single laboratory test, necessitating repeated biochemical measurements of accessible biofluids. Wearable platforms offer a practical route for repeated or continuous monitoring, whereas nanomaterial-assisted analysis of collected biofluids supports molecular profiling and analytical validation. However, small and variable sample volumes, low analyte abundance, complex matrices, and mechanical deformation can compromise the sensitivity, selectivity, and quantitative stability. Nanomaterials can address these constraints by integrating biofluid handling, signal amplification, molecular recognition, and mechanically compliant device interfaces. In this review, we describe nanomaterial-enabled metabolite sensing based on two functional layers: catalytic or affinity-based recognition and signal transduction across optical, electrochemical, and label-free fingerprinting modalities. We examined how recognition, amplification, and fluid handling are increasingly engineered into a single nanostructured interface rather than being optimized as separate elements. Beyond targeted quantification, surface-enhanced Raman scattering and nanomaterial-enhanced mass spectrometry extend sensing toward multiplexed system-level profiling at nanoliter-to-microliter volumes. Across modalities, the performance depends not on signal enhancement alone but on the coordinated control of the entire sensing chain. Other challenges include biofouling, matrix interference, calibration drift, limited durability, heterogeneous validation, and limited clinical evidence. Resolving these analytical, operational, and translational gaps may advance metabolite-guided precision medicine.